Nanoparticles in Biology Vincent Rotello, University of Massachusetts I) Introduction II) Protein Sensing II) Delivery a) DNA b) small molecules.

Transcript Nanoparticles in Biology Vincent Rotello, University of Massachusetts I) Introduction II) Protein Sensing II) Delivery a) DNA b) small molecules.

Nanoparticles in Biology

Vincent Rotello, University of Massachusetts I) Introduction II) Protein Sensing II) Delivery a) DNA b) small molecules

What is nanotechnology, and why do we care?

nanotechnology is the study of matter from 1-100 nm

What is nanotechnology, and why do we care?

nanotechnology is the study of matter from 1-100 nm for chemists: the interface between molecules and material

What is nanotechnology, and why do we care?

nanotechnology is the study of matter from 1-100 nm for chemists: the interface between molecules and material for physicists: where quantum ends and bulk begins

What is nanotechnology, and why do we care?

nanotechnology is the study of matter from 1-100 nm for chemists: the interface between molecules and material for physicists: where quantum ends and bulk begins for you: faster computers, better communication, and new approaches to medicine

What is nanotechnology, and why do we care?

What nanotechnology is not (at least so far…)

What is nanotechnology, and why do we care?

What nanotechnology is not (at least so far…)

gray goo and flesh eating nanorobots!

Noble metal nanoparticles provide a versatile building block Brust-Schiffrin reaction provides nanoparticles of regular size and shape HAuCl 4 or PdCl 2 or...

HS NaBH 4 S S S S S SS S S S S S S S S S 20 nm Brust, M.; Walker, M.; Bethell, D.; Schiffrin, D. J.; Whyman, R. J. Chem. Soc.-Chem. Commun. 1994, 801-802.

Murray place-displacement reaction allows divergent modification S S S S S SS S S S S S S S S S HS S S S S S SS S S S S S S S S S HS S S S S S SS S S S S S S S S S Ingram, R. S.; Hostetler, M. J.; Murray, R. W. J. Am. Chem. Soc. 1997, 119, 9175.

Nanoparticles provide at least two out of three (ain't bad!) SAM-covered nanoparticles provide regular shape and are the right size for biomacromolecule recognition core a 1 nm functionalized monolayer aspirin heparin 12-mer DNA 24-mer p53 bound to DNA

GSH release works with proteins (in vitro)

Verma, A.; Simard, J. M.; Worrall, J. W. E.; Rotello, V. M. J. Am. Chem. Soc, 2004, 126, 13987-13991.

Han, G.; Chari, N. S.; Verma, A.; Hong, R.; Martin, C. T.

; Rotello, V. M. Bioconjugate Chem. 2005, 16, 1356-1359.

Nanoparticles provide highly effective gene delivery agents

Cationic nanoparticles transfect mammalian cells Green fluorescent protein (GFP) plasmid transfection of 273T cells how efficient is the transfection?

what controls this efficiency?

internalized nanoparticles

Amphiphilic particles work better optimal transfection observed with ~70% cationic coverage 50

S S S S N

40 30 20

10 1

S S S S

2 0 100 85 68 63 %cationic coverage increasing chain length increases efficiency 58

S S S S N N N N

8 0 0 6 0 0 4 0 0 all of the systems are better than PEI, a popular commercial transfection agent!

next step: more complex monolayers uptake and localization tags 2 0 0 3

S S S S N N 0

1 2

MMPC

3 PEI K. Sandhu, J. Simard, C. McIntosh, S. Smith, V. Rotello, Bioconjugate. Chem., 2002, 13, 3-6.

Hong, R.; Han, G.; Kim, B.; Forbes, N. S.; Rotello, V. M J. Am. Chem. Soc., 2006, 128, 1078-1079.

Han, G.; You, C.-C.; Kim, B.-J.; Forbes, N. S.; Martin, C. T.; Rotello, V. M., Angew. Chem. 2006, 45, 3165-3169.

The Executive Summary:

Nanoparticles provide: Scaffolds for biomolecular recognition -large surface area -tunable preorganization -we can make a sensor!

Efficient delivery vectors -with tunable glutathione release -tumor penetration capabilities -and orthogonal photochemical release

Acknowledgments: Alumni: postdocs Gilles Clavier Allan Goodman Alam Syed Ulf Drechsler Amitav Sanyal Tyler Norsten Roy Shenhar Belma Erdogan Alumni: grad students Bing Nie Eric Breinlinger Michael Greaves Angelika Niemz Robert Deans Alex Cuello Trent Galow Faysal Ilhan Eunhee Jeoung Mark Gray Andy Boal Hugues d’ Cremiers Kulmeet Sandhu Kanad Das Kate Goodman Kate McKusker Kevin Bardon Joe Simard Ray Thibault Joe Carroll Oktay Uzun Nick Fischer Nandani Chari Y-M Legrand Joe Worrall Joe Fernandez Ben Frankamp Rui Hong Basar Gider Ayush Verma Ali Bayir Hiroshi Nakade Current: postdocs Chang-Cheng You “Pops” Arumugam Yuval Ofir Current: grads Hao Xu Gang Han Sudhanshu Srivastava Brian Jordan Rochelle Arviso Mrinmoy De Bappaditya Samanta Partha Ghosh Tongxiang Liu Sarit Agasti Oscar Miranda Michael Pollier Apiwat Champoosor Dap Patra Collaborators Craig Martin Mike Knapp Richard Vachet Paul Lahti “Thai” Thayumanavan Todd Emrick (PSE) Tom Russell (PSE) Mark Tuominen (Phys) Joe Jerry (Vet.An.Sci) Sallie Smith (Vet.Ani.Sci) Neil Forbes (Chem. E) Uwe Bunz (Georgia Tech) Bogdan Dragnea (IU) Graeme Cooke (Glasgow) Funding NIH NSF NSF CHM-NSEC NSF MRSEC Keck Foundation ONR DOE Army BCRP

Nanoparticles in Biology Vincent Rotello, University of Massachusetts I) Introduction II) Protein Sensing II) Delivery a) DNA b) small molecules.

Transcript Nanoparticles in Biology Vincent Rotello, University of Massachusetts I) Introduction II) Protein Sensing II) Delivery a) DNA b) small molecules.